PMID- 11395636
OWN - NLM
STAT- Publisher
LR  - 20191120
IS  - 1053-8550 (Print)
IS  - 1053-8550 (Linking)
VI  - 24
IP  - 3
DP  - 2001 May
TI  - Identification of a New Shared HLA-A2.1 Restricted Epitope From the Melanoma 
      Antigen Tyrosinase.
PG  - 212-220
AB  - SUMMARY: Tyrosinase has many advantages as a target antigen for the immunotherapy 
      of patients with melanoma because it is expressed in nearly all melanoma 
      specimens with a high degree of cellular homogeneity, and its distribution in 
      normal tissues is limited to melanocytes. To broaden our ability to direct 
      cellular immune responses against this protein, we pursued an investigation to 
      identify new shared human leukocyte antigen (HLA)-A2.1 restricted epitopes from 
      tyrosinase. Peptides were synthesized that fit a permissive HLA-A2.1 binding 
      motif and did not span common sites of polymorphism. The binding affinity of each 
      peptide to HLA-A2.1 relative to a standard peptide with intermediate binding 
      affinity was evaluated in a competitive inhibition assay. Twelve peptides were 
      selected that had binding affinities within 80% of that of the standard peptide, 
      and these were used to stimulate peripheral blood mononuclear cells (PBMC) in 
      vitro from three HLA-A2.1+ patients with metastatic melanoma. Cytotoxic T 
      lymphocytes that specifically recognized peptide-pulsed target cells as well as 
      HLA-A2.1+ tyrosinase+ melanoma cells were raised from one patient with 
      tyrosinase:8-17 (CLLWSFQTSA). To evaluate further the immunogenicity of this 
      peptide, PBMC from 23 HLA-A2.1+ patients were stimulated in vitro with 
      tyrosinase:8-17. Eleven bulk T-cell cultures demonstrated specific peptide 
      recognition, and six of these also recognized HLA-A2.1+ tyrosinase+ melanoma 
      cells. These data suggest that tyrosinase:8-17 may be clinically useful for the 
      treatment of patients with melanoma.
FAU - Riley, John P
AU  - Riley JP
AD  - Surgery Branch, National Cancer Institute, National Institutes of Health, 
      Bethesda, Maryland, U.S.A.
FAU - Rosenberg, Steven A
AU  - Rosenberg SA
FAU - Parkhurst, Maria R
AU  - Parkhurst MR
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Immunother (1991)
JT  - Journal of immunotherapy : official journal of the Society for Biological Therapy
JID - 9102704
EDAT- 2001/06/08 10:00
MHDA- 2001/06/08 10:00
CRDT- 2001/06/08 10:00
PHST- 2001/06/08 10:00 [pubmed]
PHST- 2001/06/08 10:00 [medline]
PHST- 2001/06/08 10:00 [entrez]
PST - ppublish
SO  - J Immunother (1991). 2001 May;24(3):212-220.